The most common form of the cancer originating in the brain is the most aggressive and advanced Stage IV variety called glioblastoma, Lower grade gliomas often progress to later become Stage IV GBMs. Currently, the differentiation of disease recurrence during the standard management of this life-threatening disease is very complex and difficult to distinguish from tumor necrosis following radiation therapy, making treatment and definition of risk very complex and inaccurate
The current standard treatment regimen for GBM includes surgical resection, external beam radiation, and oral chemotherapy. However, life expectancy is typically only 12-16 months due to the challenges to treatment including the tentacle-like protrusions of the tumor which are difficult to excise and the limited drug access due to the blood-brain barrier. Given the limited effectiveness of treatment and likelihood of recurrence, it is important to closely monitor patients following treatment. At present MRI imaging is unable to adequately discriminate between radio-necrosis due to radiation treatment and recurrence of the solid brain tumor. As such practitioners are forced to empirically assess patient progress by methods such as MRI or are required to use tumor biopsies for advanced PET and SPECT imaging studies. These processes have significant impact on patient welfare and cost of care.
Standard treatment regimens and the challenges for treatment of other WHO Grade III and Grade IV tumors are similar.
Gliolan, of which 5-ALA is an active ingredient, is approved in Europe for use as a reagent to enable the differential visualization of tumor tissue vs. normal brain tissue under fluorescence and permit more complete resection rates by the neurosurgeon. High-grade brain tumors (WHO-grade III and IV, e.g., GBM, gliosarcoma, anaplastic astrocytoma) metabolize 5-ALA to fluorescent porphyrins at rates higher then normal brain tissue and low-grade brain tumors (WHO grade I and II, e.g., medulloblastoma, oligdendroglioma) and therefore have increased fluorescence. However, it is unknown whether 5-ALA signal can be detected non-invasively.
Accordingly, there remains a need for simple, non-invasive methods to detect WHO Grade III and IV brain tumors and assess the presence and recurrence of such tumors in a variety of subjects.
In addition, there remains a general need for simple, non-invasive methods to detect and assess all types of solid tumors and to detect response to treatment or breakthrough resulting in disease recurrence.